Neuroscience
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In the retina, ON- and OFF-type bipolar cells are classified by subtype-specific center responses, which are attributed to differences in glutamate receptor subtypes. However, the mechanisms by which ON- and OFF-type bipolar cells generate subtype-specific surround responses remain unclear. One hypothesis for surround responses is that intracellular Cl concentrations ([Cl-]i) are set at different levels to achieve opposite polarities for GABA responses in ON- and OFF-type bipolar cells. ⋯ Strong NKCC1 activity increased [Cl-]i in rod (ON-) type bipolar cells, while that of KCC2 decreased [Cl-]i in OFF-type bipolar cells. We also confirmed the presence of a [Cl-]i gradient between dendrites and axon terminals in rod (ON-type) bipolar cells. Thus, the subtype-specific control of [Cl-]i is achieved by the activity of NKCC1 relative to that of KCC2 and appears to influence the polarity of surround responses.
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NSAIDs are the drugs most commonly used to alleviate pain. Despite being a heterogeneous group of compounds, all of them share a mechanism of action based on blockade of COXs enzymes, which confers them anti-inflammatory and analgesic properties. Diclofenac is a NSAID with preferred activity on COX-2 isozymes, but additionally, other targets may be implicated in its analgesic activity. ⋯ Depressant actions of both compounds were strongly reduced after Kv7 channel blockade with XE-991, indicating the implication of these channels in the observed effects. Flupirtine, but not diclofenac, also reduced action potential firing of dorsal horn neurons in response to electrical activation of nociceptive afferents, suggesting differences in the actions of both compounds on Kv7 channel configurations present in sensory areas of the cord. Results demonstrate previously unknown central actions of diclofenac on Kv7 channels located in spinal circuits, expanding the knowledge about its pharmacological actions.
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Androgen receptor (AR) is abundantly expressed in the preoptico-hypothalamic area, bed nucleus of stria terminalis, and medial amygdala of the brain where androgen plays an important role in regulating male sociosexual, emotional and aggressive behaviors. In addition to these brain regions, AR is also highly expressed in the hippocampus, suggesting that the hippocampus is another major target of androgenic modulation. It is known that androgen can modulate synaptic plasticity in the CA1 hippocampal subfield. ⋯ These effects were successfully reversed by treatment with either aromatizable androgen T or non-aromatizable androgen DHT. Furthermore, administration of the AR-antagonist flutamide in intact rats showed similar changes to those in OCX rats, suggesting that androgens affect the excitability of CA1 pyramidal neurons possibly by acting on the AR. Our current study potentially clarifies the role of androgen in enhancing the basal excitability of the CA1 pyramidal neurons, which may influence selective neuronal excitation/activation to modulate certain hippocampal functions.
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Parkinson's disease is a disorder of adult onset involving the progressive degeneration of selective portions of the central nervous system. It is known that mitochondrial dysfunction is involved in the pathogenesis of PD. Given that PGC-1α induces proliferation of mitochondria via transcription regulation, it is possible that PGC-1α pathway dysregulation is involved in PD pathogenesis. ⋯ Expression of CoxIV, SDHA and Tomm20 also significantly decreased in the ventral midbrains of 10-month-old PGC-1α null mice. Thus, PGC-1α KO in mice induced dopaminergic neuron degeneration in the SNpc and DA deficits in the striatum in an age-dependent manner. Progressive impairment of motor coordination in an age-dependent manner was correlated to the extent of nigrostriatal dopaminergic pathway degeneration and mitochondrial dysfunction.
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Deep brain stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. It acts by altering brain networks and facilitating synaptic plasticity. For enhancing cognitive functions, the central thalamus (CT) has been shown to be a potential DBS target. ⋯ Concurrent with enhanced learning performance, bilateral CT-DBS resulted in alteration in the functional connectivity of brain networks determined by resting-state fMRI. Western blot analyses showed that the protein level of both dopamine D1 and α4-nicotinic acetylcholine receptors was increased, and dopamine D2 receptor was decreased. These data suggest that CT-DBS can enhance cognitive performance as well as brain connectivity through the modulation of synaptic plasticity, such that CT is a target providing high potential for the remediation of acquired cognitive learning and memory disabilities.